grant
Targeting FOXA2/AP-1 axis to overcome lineage plasticity and therapy resistance in castration-resistant prostate cancer
Organization UNIVERSITY OF MASSACHUSETTS BOSTONLocation BOSTON, UNITED STATESPosted 21 Feb 2025Deadline 31 Jan 2030
NIHUS FederalResearch GrantFY2026ACSL1ACSL1 GeneAOF2AP-1AP-1 Enhancer-Binding ProteinAP1AP1 proteinASCL1ASCL1 geneASCL1 proteinASH1Achaete-Scute Complex Homolog-Like 1 ProteinAchaete-Scute Complex-Like 1 ProteinAchaete-Scute Homolog 1 ProteinActivator Protein-1AdenocarcinomaAdenocarcinoma CellAndrogen ReceptorAutomobile DrivingBasal Transcription FactorBasal transcription factor genesBindingCancer PatientCell BodyCell LineCellLineCellsChromatinClinical TrialsCollaborationsCombined Modality TherapyDataDevelopmentEnhancer-Binding Protein AP1EnhancersEventGene TranscriptionGeneral Transcription Factor GeneGeneral Transcription FactorsGenetic TranscriptionGoalsHASH1HASH1 proteinHistonesHumanJUNKDM1AKDM1A geneLSD1Lysine-Specific Demethylase 1Lysine-Specific Demethylase 1AMASH 1 proteinMASH1MASH1 proteinMalignant AdenomaMalignant Glandular CellMalignant neoplasm of prostateMalignant prostatic tumorMammalian Achaete-Scute Homolog 1MediatingMiceMice MammalsModelingModern ManMolecularMolecular InteractionMultimodal TherapyMultimodal TreatmentMurineMusNeuroendocrine Prostate CancerNucleosomesPDX modelPatient derived xenograftPatient outcomePatient-Centered OutcomesPatient-Focused OutcomesPatientsPeptidesProcessProstate CAProstate CancerProstate malignancyProtein FamilyPublishingRNA ExpressionResearchResistanceResistance developmentResistant developmentRoleSeriesSiteStrains Cell LinesTestingTherapeuticTranscriptionTranscription Factor AP-1Transcription Factor Proto-OncogeneTranscription factor genesTransgenic MiceTranslatingTumor CellXenograft Modelandrogen independent prostate cancerandrogen indifferent prostate cancerandrogen insensitive prostate cancerandrogen resistance in prostate cancerandrogen resistant prostate cancercastration resistant CaPcastration resistant PCacastration resistant prostate cancercell transformationcombination therapycombined modality treatmentcombined treatmentcultured cell linedemethylationdesigndesigningdetermine efficacydeveloping resistancedevelopmentaldrivingefficacy analysisefficacy assessmentefficacy determinationefficacy evaluationefficacy examinationevaluate efficacyexamine efficacyhormone refractory prostate cancerimprovedinhibitorinsightjun Oncogenemouse modelmulti-modal therapymulti-modal treatmentmurine modelneoplastic celloverexpressoverexpressionpatient derived xenograft modelpatient oriented outcomespre-clinicalpreclinicalprogramsprostate cancer cellprostate cancer cell lineprostate cancer progressionprostate cancer resistant to androgenprostate tumor cellresistantresponsesmall molecular inhibitorsmall molecule inhibitorsocial roletargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttranscription factortranscriptional reprogrammingtransformed cellstreatment effecttreatment strategytumorxenograft transplant modelxenotransplant model
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PROJECT SUMMARY
Background: Prostate cancer (PCa) can develop resistance to androgen receptor (AR)-targeted therapies and
progress to AR-indifferent stages, such as NEPC or DNPC, through lineage plasticity. While several driver
transcription factors for AR-indifferent PCa have been identified, the mechanisms by which lineage-specific
developmental…
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